57 research outputs found

    Investigating the role of spindle checkpoint mutations in colorectal cancer

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    The genome sequence of the small elephant hawk moth, Deilephila porcellus (Linnaeus, 1758)

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    We present a genome assembly from an individual male Deilephila porcellus (the small elephant hawk moth; Arthropoda; Insecta; Lepidoptera; Sphingidae). The genome sequence is 402 megabases in span. The majority of the assembly (99.99%) is scaffolded into 29 chromosomal pseudomolecules, with the Z sex chromosome assembled

    Archaeology and contemporary death: Using the past to provoke, challenge and engage

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    While death is universal, reactions to death and ways of dealing with the dead body are hugely diverse, and archaeological research reveals numerous ways of dealing with the dead through time and across the world. In this paper, findings are presented which not only demonstrate the power of archaeology to promote and aid discussion around this difficult and challenging topic, but also how our approach resulted in personal growth and professional development impacts for participants. In this interdisciplinary pilot study, archaeological case studies were used in 31 structured workshops with 187 participants from health and social care backgrounds in the UK, to explore their reactions to a diverse range of materials which documented wide and varied approaches to death and the dead. Our study supports the hypothesis that the past is a powerful instigator of conversation around challenging aspects of death, and after death care and practices: 93% of participants agreed with this. That exposure to archaeological case studies and artefacts stimulates multifaceted discourse, some of it difficult, is a theme that also emerges in our data from pre, post and follow-up questionnaires, and semi-structured interviews. The material prompted participants to reflect on their biases, expectations and norms around both treatment of the dead, and of bereavement, impacting on their values, attitudes and beliefs. Moreover, 87% of participants believed the workshop would have a personal effect through thinking differently about death and bereavement, and 57% thought it would impact on how they approached death and bereavement in their professional practice. This has huge implications today, where talk of death remains troublesome, and for some, has a near-taboo status–‘taboo’ being a theme evident in some participants’ own words. The findings have an important role to play in facilitating and normalising discussions around dying and bereavement and in equipping professionals in their work with people with advanced illness

    The genome sequence of the brown china-mark moth, Elophila nymphaeata (Linnaeus, 1758)

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    We present a genome assembly from an individual female Elophila nymphaeata (the Brown China-mark moth; Arthropoda; Insecta; Lepidoptera; Crambidae). The genome sequence is 734.1 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,079 protein coding genes

    Iyengar yoga for Long Covid: Pilot study results

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    The Iyengar Yoga (UK) Long Covid pilot project ran for 10 weeks between October December 2021. 55 adults (ranging from 22-69 years of age) suffering from Long Covid participated in the programme which saw one student having a weekly online private yoga sessions with three qualified Iyengar Yoga teachers, supervised by a senior therapy teacher. The project was supervised by Lois Steinberg and the basic recommended asana sequence available on the IY(UK) website. 115 IY(UK) teachers (with a pool of 19 cover teachers) volunteered their time in return for professional development training provided as part of the programme. It can be concluded that the programme was effective in improving both physical and mental well-being for those suffering from Long Covid

    Toluene inhalation exposure for 13 weeks causes persistent changes in electroretinograms of Long–Evans rats

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    Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000 ppm toluene by inhalation (6 hr/d, 5 d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m2) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000 ppm toluene for 4 weeks were tested approximately 1 year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1 year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensitive to organic solvent exposure than the rat visual cortex

    Effect of Pretreatment Method on the Nanostructure and Performance of Supported Co Catalysts in Fischer−Tropsch Synthesis

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    ABSTRACT: Understanding precursor transformation to active catalysts is crucial to heterogeneous Fischer−Tropsch (FT) catalysis directed toward production of hydrocarbons for transportation fuels. Despite considerable literature on FT catalysis, the effect of pretreatment of supported cobalt catalysts on cobalt dispersion, dynamic atomic structure, and the activity of the catalysts is not well understood. Here we present systematic studies into the formation of active catalyst phases in supported Co catalyst precursors in FT catalysis using in situ environmental (scanning) transmission electron microscopy (E(S)TEM) with single-atom resolution under controlled reaction environments for in situ visualization, imaging, and analysis of reacting atomic species in real time, EXAFS, XAS, DRIFTS analyses, and catalytic activity measurements. We have synthesized and analyzed dried reduced (D) and dried calcined reduced (DC) Co real catalysts on reducible and nonreducible supports, such as SiO2, Al2O3, TiO2, and ZrO2. Comparisons of dynamic in situ atomic structural observations of reacting single atoms, atomic clusters, and nanoparticles of Co and DRIFTS, XAS, EXAFS, and catalytic activity data of the D and DC samples reveal in most cases better dispersion in the D samples, leading to a larger number of low-coordination Co0 sites and a higher number of active sites for CO adsorption. The experimental findings on the degree of reduction of D and 27 DC catalysts on reducible and nonreducible supports and correlations between hexagonal (hcp) Co sites and the activity of the catalysts generate structural insights into the catalyst dynamics, important to the development of efficient FT catalysts

    IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans

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    Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs. In contrast, disruption of motile cilia function causes subfertility, disruption of the left-right body axis, and recurrent airway infections with progressive lung damage. In this work, we characterize allele specific phenotypes resulting from IFT74 dysfunction in human and mice. We identified two families carrying a deletion encompassing IFT74 exon 2, the first coding exon, resulting in a protein lacking the first 40 amino acids and two individuals carrying biallelic splice site mutations. Homozygous exon 2 deletion cases presented a ciliary chondrodysplasia with narrow thorax and progressive growth retardation along with a mucociliary clearance disorder phenotype with severely shorted cilia. Splice site variants resulted in a lethal skeletal chondrodysplasia phenotype. In mice, removal of the first 40 amino acids likewise results in a motile cilia phenotype but with little effect on primary cilia structure. Mice carrying this allele are born alive but are growth restricted and developed hydrocephaly in the first month of life. In contrast, a strong, likely null, allele of Ift74 in mouse completely blocks ciliary assembly and causes severe heart defects and midgestational lethality. In vitro studies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia resulting from increased mechanical stress and repair needs could account for the motile cilia phenotype observed in human and mice

    IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans

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    Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs. In contrast, disruption of motile cilia function causes subfertility, disruption of the left-right body axis, and recurrent airway infections with progressive lung damage. In this work, we characterize allele specific phenotypes resulting from IFT74 dysfunction in human and mice. We identified two families carrying a deletion encompassing IFT74 exon 2, the first coding exon, resulting in a protein lacking the first 40 amino acids and two individuals carrying biallelic splice site mutations. Homozygous exon 2 deletion cases presented a ciliary chondrodysplasia with narrow thorax and progressive growth retardation along with a mucociliary clearance disorder phenotype with severely shorted cilia. Splice site variants resulted in a lethal skeletal chondrodysplasia phenotype. In mice, removal of the first 40 amino acids likewise results in a motile cilia phenotype but with little effect on primary cilia structure. Mice carrying this allele are born alive but are growth restricted and developed hydrocephaly in the first month of life. In contrast, a strong, likely null, allele of Ift74 in mouse completely blocks ciliary assembly and causes severe heart defects and midgestational lethality. In vitro studies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia resulting from increased mechanical stress and repair needs could account for the motile cilia phenotype observed in human and mice

    The genome of the yellow potato cyst nematode, Globodera rostochiensis, reveals insights into the basis of parasitism and virulence

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    BACKGROUND: The yellow potato cyst nematode, Globodera rostochiensis, is a devastating plant pathogen of global economic importance. This biotrophic parasite secretes effectors from pharyngeal glands, some of which were acquired by horizontal gene transfer, to manipulate host processes and promote parasitism. G. rostochiensis is classified into pathotypes with different plant resistance-breaking phenotypes. RESULTS: We generate a high quality genome assembly for G. rostochiensis pathotype Ro1, identify putative effectors and horizontal gene transfer events, map gene expression through the life cycle focusing on key parasitic transitions and sequence the genomes of eight populations including four additional pathotypes to identify variation. Horizontal gene transfer contributes 3.5 % of the predicted genes, of which approximately 8.5 % are deployed as effectors. Over one-third of all effector genes are clustered in 21 putative ‘effector islands’ in the genome. We identify a dorsal gland promoter element motif (termed DOG Box) present upstream in representatives from 26 out of 28 dorsal gland effector families, and predict a putative effector superset associated with this motif. We validate gland cell expression in two novel genes by in situ hybridisation and catalogue dorsal gland promoter element-containing effectors from available cyst nematode genomes. Comparison of effector diversity between pathotypes highlights correlation with plant resistance-breaking. CONCLUSIONS: These G. rostochiensis genome resources will facilitate major advances in understanding nematode plant-parasitism. Dorsal gland promoter element-containing effectors are at the front line of the evolutionary arms race between plant and parasite and the ability to predict gland cell expression a priori promises rapid advances in understanding their roles and mechanisms of action.SE-vdA is supported by BBSRC grant BB/M014207/1. Sequencing was funded by BBSRC grant BB/F000642/1 to the University of Leeds and grant BB/F00334X/1 to the Wellcome Trust Sanger Institute). DRL was supported by a fellowship from The James Hutton Institute and the School of Biological Sciences, University of Edinburgh. GK was supported by a BBSRC PhD studentship. The James Hutton Institute receives funding from the Scottish Government. JAC and NEH are supported by the Wellcome Trust through its core funding of the Wellcome Trust Sanger Institute (grant 098051). This work was also supported by funding from the Canadian Safety and Security Program, project number CRTI09_462RD
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